Abstract
The novel, highly contagious coronavirus SARS-CoV-2 spreads rapidly throughout the world, leading to a deadly pandemic of a predominantly respiratory illness called COVID-19. Safe and effective anti-SARS-CoV-2 vaccines are urgently needed. However, emerging immunological observations show hallmarks of significant immunopathological characteristics and dysfunctional immune responses in patients with COVID-19. Combined with existing knowledge about immune responses to other closely related and highly pathogenic coronaviruses, this could forebode significant challenges for vaccine development, including the risk of vaccine failure. Animal data from earlier coronavirus vaccine efforts indicate that elderly people, most at risk from severe COVID-19 disease, could be especially at risk from immunopathologic responses to novel coronavirus vaccines. Bacterial “new old friends” such as Bacille Calmette-Guérin (BCG) or Mycobacterium obuense have the ability to elevate basal systemic levels of type 1 cytokines and immune cells, correlating with increased protection against diverse and unrelated infectious agents, called “trained immunity.” Here we describe dysfunctional immune responses induced by coronaviruses, representing potentially difficult to overcome obstacles to safe, effective vaccine development for COVID-19, and outline how trained immunity could help protect high risk populations through immunomodulation with BCG and other “new old friends.”
Highlights
In recent months, a novel severe acute respiratory syndrome (SARS) coronavirus (CoV), SARSCoV-2, which causes COVID-19, has spread rapidly throughout the world [1]
The unprecedented pandemic seriously challenges the world’s health care systems and available hospital capacities to treat seriously ill patients. These challenges are amplified by frequent SARS-CoV-2 infection of healthcare workers (HCW), leading to hospital-acquired infection of HCW and patients, and significant mortality within that group [2]
The suggestion that a dysfunctional immune response is at the heart of COVID-19 pathology is further supported by the recent finding that, compared to patients with moderate disease, significantly reduced frequencies of CD8+ T cells, as well as diminished frequencies of CD4+ and CD8+ T cell subsets with activated differentiated memory/effector phenotype and migratory capacity, are found in peripheral circulation of patients with severe COVID-19 [90]
Summary
A novel severe acute respiratory syndrome (SARS) coronavirus (CoV), SARSCoV-2, which causes COVID-19, has spread rapidly throughout the world [1]. It was recently shown that a patient with mild to moderate COVID-19 symptoms had a broad-based robust immune response across different immune cell types, which was associated with rapid recovery [68] This observational study identified the presence of activated CD4+ T cells, CD8+ T cells, and follicular helper T cells in the blood, along with increased antibody-secreting cells and IgM and IgG antibodies. The suggestion that a dysfunctional immune response is at the heart of COVID-19 pathology is further supported by the recent finding that, compared to patients with moderate disease, significantly reduced frequencies of CD8+ T cells, as well as diminished frequencies of CD4+ and CD8+ T cell subsets with activated differentiated memory/effector phenotype and migratory capacity, are found in peripheral circulation of patients with severe COVID-19 [90]
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